The objectives of this project are to assess the involvement of human retroviruses in chronic-progressive myeloneuropathy termed HTLV-I-related myelopathy/tropical spastic paraparesis (HAM/TSP) and multiple sclerosis. These investigations have two major components: 1) the molecular/virological identification of the virus(es) that are associated with the pathogenesis of these disorders, and 2) the immunological response of the host to the identified agent(s). Parallel studies are being conducted in normal carriers of HTLV-I. Human retroviruses are isolated from cells in the peripheral blood and cerebrospinal fluid. The polymerase chain reaction is used to detect and characterize viral genes in lymphocytes and in the central nervous system. These viral genomes are being cloned and sequenced. Tissue sections from spinal cord and brain from individuals with neurological diseases also are analyzed for the presence of retroviral DNA by in situ hybridization. Immune reactivity to these agents are characterized by demonstrating virus-specific cytotoxic T cell (CTL) responses in these patients, as well as lymphoproliferative responses. CTL are generated from long-term cultures. In addition, the presence of CTL in the peripheral blood of individuals with active infection is being examined. The responding cells and the antigenic specificity of the response are being characterized.